Aches, pains, and discomfort are common problems. For example, ibuprofen has the chemical name 2-(4-Isobutylphenyl)propionic acid and is a well-tolerated drug possessing analgesic, antipyretic and anti-inflammatory activities (Merck Index, 11th edition, no. 4812). Current treatments for such pains are pills, gelatin capsules, and powder capsules that make their way through the gastrointestinal tract to the circulatory system. Such a traversal of the various organs in the body depletes the active ingredients in the liver, stomach and intestines while exposing the tissues of those organs to the effects of the active ingredient. Some patients have experienced stomach irritation and ulcers from orally ingested treatments. Some adults and many young children also have difficulty swallowing such pills and actively seek other forms of such medication. Other ways to administer analgesic medications and treatments include subcutaneous injections and nasal sprays. Subcutaneous injections are painful and difficult to self-administer. Nasal sprays have hitherto experienced stability problems with the dispersion and integrity of the active ingredients.
A number of analgesic and therapeutic medications and homeopathic treatments are known and reflected in one or more patents. The interest in homeopathic and/or herbal medicines has increased recently due in part to the lower cytotoxicity associated with such medications. Homeopathy is commonly used to mean a system of medicine based on the use of infinitesimal doses of medicines capable of producing symptoms similar to those of the disease treated. By stimulating a subject's natural defenses (i.e., increasing the symptoms) the subject will be motivated or directed towards homeostasis, since one's symptoms are actually efforts of the organism to reestablish homeostasis or balance. Homeopathic treatment encompasses some forms of natural materials including plant extracts and the like. However, some natural plant extracts are not necessarily homeopathic treatments as the extracts themselves do not stimulate disease or disorder symptoms but rather inhibit their onset or severity.
For example, ginger has been used with some success for relief of nausea. The administration of 1,000 to 2,000 mg of ginger orally by tablet has been found to effectively reduce nausea in the case of motion sickness.
Another example is feverfew, an herb that is widely available and has been investigated in modem times. Historically, feverfew is known to have been used in the treatment of fevers, from whence it derives its name, and also in rheumatic conditions. Fresh feverfew leaves have sometimes been chewed by subjects wishing to rid themselves of migraine. However, a common adverse effect reported by those who have used this technique is the generation sores in the mouth and sensitization of oral tissues. Additionally, many patients find this mode of administration to be crude and unpleasant. Feverfew tablets or capsules do not expose the mouth tissues to the same effects as chewed leaves and have been employed by practitioners of herbal medicine.
The use of feverfew for treatment of migraines is known. For example, U.S. Pat. No. 6,103,218 to Brucker, et al. discloses a composition and delivery system in which feverfew is delivered in the form of an aqueous nasal spray for the relief of migraine headaches.
The use of a combination of feverfew and ginger for the treatment migraines in a sublingual form is known. U.S. Patent Application Publication No. 2006/0222722 to Roberts, et al. discloses sublingual methods of treating arthritis by administering a composition including feverfew and ginger. The reference lacks disclosure of combining ibuprofen in the composition and moreover, the ability to make a stable, sublingual pharmaceutical spray composition in which an ingredient of the composition is a stable, water-soluble ibuprofen.
The combination of analgesics and feverfew dissolved in aqueous mediums for treating aches and/or pains has also been suggested. U.S. Pat. No. 6,770,263 to Brucker discloses a composition that comprises an aqueous medium in which feverfew and an analgesic are dissolved or dispersed. One problem associated with such a composition is that the analgesic, such as ibuprofen, is not stable for extended periods and through a wide variety of temperature extremes.
Liquid formulations for delivering medicaments and herbal therapeutic agents is not, however, a new development. Biologically active agents such as nutritional supplements, hormones, and a variety of pharmaceutical preparations are typically provided in oral (liquids or solids) or injectable dosage formulations. There are, however, difficulties with maintaining stability of the solution or dispersion without precipitation and with maintaining efficacy of the ingredients associated with this formulation.
One manner to overcome the limitations discussed above is to produce granulates from powder mixtures. For purposes of administration, these granulates are usually converted into tablets, enclosed in capsules or in sachets. It has also been long known that granules or tablets can be coated with films, which can serve to delay the release of the active ingredient they contain, disguise an unpleasant taste, and/or improve the stability of the composition. A major limitation of the use of such coated granulates in liquid formulations is that it has been difficult to obtain particles of an appropriate size to enable them to be easily suspended and kept in suspension in the fluid vehicle.
One manner of producing granules involves the use of a conventional mixer-granulator, which consists of a vessel, which may be of varying shape, equipped with an agitator that keeps the powder moving while the granulation fluid is being added. The motion is slow and the resulting globules, even though suitable for making conventional dosage forms such as tablets or capsules, does not possess the density, shape and particle-size distribution suitable for subsequent coating.
Unlike conventional mixer-granulators, extruder-spheronizers can produce spherical particles of homogeneous sizes and even shapes and surfaces. The limitation that prevents their application to microgranulates suitable for liquid suspensions is the average product size, which is rarely smaller than 1-2 mm and in any case never smaller than 500 μm.
It would be desirable to have a method for producing analgesic and similar pain-treating compositions that could produce particles of very fine size in a stable, aqueous formulation.
It would also be desirable to have a spray formulation that would require low concentrations of active ingredients for contact with sublingual mucosal tissues.